The Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) at the University of California San Diego (UCSD) Stroke Center currently applies the resources of 4 Cores to conduct 3 interrelated clinical trials designed to meet the overarching SPOTRIAS goal of increasing the number of thrombolytic-treated patients. Over the course of the 5-year renewal period, we propose to move this agenda forward with 6 new clinical trials: (1) Intravascular Cooling in the Treatment of Stroke-Caffeinol (ICTuS-C), which builds on the ongoing hypothermia research track of ICTuS-L, evolving from demonstration of the feasibility and safety of intravascular cooling in combination with thrombolysis to collaborative assessment, with Houston SPOTRIAS, of the safety, feasibility, and early efficacy of the endovascular induction of hypothermia and caffeinol in acute ischemic stroke patients presenting within the 3-hour window;(2) Transcranial Ultrasound in Acute Stroke, which builds on the ongoing ultrasound imaging research track to study the potential of diagnostic ultrasound in combination with rt-PA and/or ultrasound contrast agent microbubbles on image-guided transcranial thrombolysis;(3) Stroke Team Remote Evaluation Using a Digital Observation Camera - Optimizing Practitioners'Use in Stroke (STRokE DOC OPUS), which builds on the ongoing audio-visual telemedicine research track to explore the utility of remote telemedicine consultations for acute stroke by determining whether our pioneering hub-and-spoke model can be replicated in other communities and whether next-generation, optimized technology will increase use of the STRokE DOC system in areas with limited access to Internet-based technology;(4) Counterpulsation to Upgrade Forward Flow in Stroke (CUFFS), a new pilot assessment of the tolerability, feasibility, and safety of noninvasive external counterpulsation (ECP) in acute ischemic stroke patients within 0-48 hours of symptom onset;(5) Safety of tPA plus Transcranial Emission of Low-Energy Lasers for Acute Stroke Recovery (StELLAR), the first combination study of the NeuroThera Laser System with rt-PA;and (6) Spot Sign for Predicting and Treating ICH Growth (STOP IT), a study of acute intracerebral hemorrhages to determine the sensitivity and specificity of CT angiography for the prediction of hematoma growth and to test the feasibility of CT angiography for the guidance of hemostatic therapy. Altogether, our SPOTRIAS proposal for the renewal period aims to integrate and synthesize further the considerable strengths of the UCSD Stroke Center in conducting translational research that ultimately benefits stroke victims within our geographical practice range and worldwide as we treat more patients under 2 hours and explore new ways to safely and effectively treat other, guideline-ineligible patients outside the 3-hour rt-PA window, including through improved patient selection and stratification and additional treatments combined with and potentially augmenting thrombolysis.